One-carbon metabolism modulates miR-29a-DNA methylation crosstalk in Alzheimer's disease

Abstract

Introduction: Alzheimer's disease (AD)'s multifactorial nature stresses the role of epigenetics in affecting different pathological pathways. We demonstrated that one-carbon metabolism epigenetically impacts AD-like phenotype. Here, we investigated the crosstalk between methylation and microRNAs in AD.

Methods: We altered one-carbon metabolism to induce hypo- and hyper-methylation, in SK-N-BE neuroblastoma cells and TgCRND8 mice. miRNAs were profiled through a polymerase chain reaction array, then we focused on miR-29a expression and methylation of its genomic locus. Finally, we assessed miR-29a expression and methylation in the brain of AD subjects.

Results: MiR-29a was repressed in hypomethylating and expressed in hypermethylating conditions. The expression of miR-29a and of its target, BACE1, was inversely correlated.

Discussion: We demonstrated for the first time that miR-29a is modulated by one-carbon metabolism through DNA methylation, disclosing the molecular mechanisms regulating BACE1 expression in AD. These data confirm miR-29a's protective role in AD and support miR-29a as a potential biomarker for AD.

Keywords: Alzheimer's disease; DNA methylation; epigenetics; microRNAs; mir‐29a; non‐CPG methylation; one‐carbon metabolism.